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NCT02186652: PAN01

PK Study With Pantoprazole in Obese Children and Adolescents

Completed Phase 1 Results posted Last updated 17 September 2019
What this trial tests

Phase 1 trial testing Pantoprazole in Gastroesophageal Reflux Disease in 41 participants. Completed in 13 September 2015.

Timeline
4 June 2014
Primary endpoint
13 September 2015
13 September 2015

Quick facts

Lead sponsorPhillip Brian Smith
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposebasic science
Enrollment41
Start date4 June 2014
Primary completion13 September 2015
Estimated completion13 September 2015
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Phillip Brian Smith — full company profile →

Who can join

Adults 6 to 17, any sex, with Gastroesophageal Reflux Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Cmax). Primary · pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, \& 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Cmax.

GroupValue95% CI
Pantoprazole 6-11 Year Old4.27± 1.43
Pantoprazole 12-17 Year Old4.1± 1.18
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Tmax). Primary · pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, \& 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Tmax.

GroupValue95% CI
Pantoprazole 6-11 Year Old2.31.5 – 3
Pantoprazole 12-17 Year Old2.51.5 – 8
PK Sampling Primary · Pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing

Total number of fresh plasma samples (all participants)

GroupValue95% CI
Pantoprazole 6-11 Year Old11± 2
Pantoprazole 12-17 Year Old11± 2
Drug Concentration in Plasma Samples Primary · Pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing

Concentration of panto in plasma and concentration of panto sulfone in plasma

Pantoprazole
GroupValue95% CI
Pantoprazole 6-11 Year Old1558± 1584.6
Pantoprazole 12-17 Year Old1626.1± 1545.2
Pantoprazole Sulfone
GroupValue95% CI
Pantoprazole 6-11 Year Old94.7± 49.1
Pantoprazole 12-17 Year Old88.7± 36.8
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC). Primary · pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, \& 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report AUC TBW.

GroupValue95% CI
Pantoprazole 6-11 Year Old8.87± 4.00
Pantoprazole 12-17 Year Old11.56± 4.81
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC). Primary · pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, \& 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report AUC LBW.

GroupValue95% CI
Pantoprazole 6-11 Year Old5.73± 2.48
Pantoprazole 12-17 Year Old6.82± 2.70
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (CL/F). Primary · pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, \& 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report CL/F TBW.

GroupValue95% CI
Pantoprazole 6-11 Year Old0.14± 0.07
Pantoprazole 12-17 Year Old0.10± 0.04
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F). Primary · pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, \& 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Vd/F TBW.

GroupValue95% CI
Pantoprazole 6-11 Year Old0.16± 0.05
Pantoprazole 12-17 Year Old0.14± 0.04
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F). Primary · pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, \& 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Vd/F LBW.

GroupValue95% CI
Pantoprazole 6-11 Year Old0.25± 0.09
Pantoprazole 12-17 Year Old0.25± 0.07
The CYP2C19 Genotype and Its Association With CYP2C19 Phenotype Secondary · 0, 1, 2, 3, 4, 6, 8, 12 hours post-dose

To examine the association of CYP2C19 genotype and its association with CYP2C19 phenotypes. To characterize the ability of the CYP2C19 genotype to predict pantoprazole plasma clearance, a correlation with CYP2C19 phenotype was explored using both standard linear and nonlinear regression techniques and their respective tests for significance and goodness of fit. In addition, the impact of all covariates on pantoprazole systemic exposure and apparent plasma clearance (e.g., demographic determinants of extent of obesity such as the waist:hip ratio, CYP2C19 genotype, BMI, and REE) was explored usi

GroupValue95% CI
*2*2 Allele1.29NA – NA
*1/*2 Allele6.002.64 – 11.62
*1/*1 Allele or *1/*17 Allele8.974.66 – 16.71

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were followed up to 10 days post study dose.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

6-11 Year Old Adverse Events
Serious: 0/19 (0%)
Deaths: 0/19
12-17 Year Old Adverse Events
Serious: 0/22 (0%)
Deaths: 0/22
Other adverse events (8 terms — click to expand)

ReactionSystem6-11 Year Old Adverse Events12-17 Year Old Adverse Eve…
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Urinary Tract InfectionInfections and infestations
LacerationInjury, poisoning and procedural complications
HeadacheNervous system disorders
nephrolithiasisRenal and urinary disorders
DysmenorrhoeaReproductive system and breast disorders
HiccupsRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT02186652 adverse events section.

Sponsor's own description

Multicenter, comparative single-dose pharmacokinetic (PK) study

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Drug interventions for the treatment of obesity in children and adolescents.
    Mead E, Atkinson G, Richter B, Metzendorf MI, et al · · 2016 · cited 71× · PMID 27899001 · DOI 10.1002/14651858.cd012436
  2. Optimizing operational efficiencies in early phase trials: The Pediatric Trials Network experience.
    England A, Wade K, Smith PB, Berezny K, et al · · 2016 · cited 30× · PMID 26968616 · DOI 10.1016/j.cct.2016.03.002
  3. Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures.
    Shakhnovich V, Smith PB, Guptill JT, James LP, et al · · 2018 · cited 25× · PMID 29389444 · DOI 10.1016/j.jpeds.2017.10.011
  4. A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents.
    Shakhnovich V, Brian Smith P, Guptill JT, James LP, et al · · 2018 · cited 16× · PMID 30097906 · DOI 10.1007/s40272-018-0305-1
  5. Physiologically-based pharmacokinetic modeling of pantoprazole to evaluate the role of CYP2C19 genetic variation and obesity in the pediatric population.
    Thompson EJ, Jeong A, Helfer VE, Shakhnovich V, et al · · 2024 · cited 5× · PMID 38837864 · DOI 10.1002/psp4.13167

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