PK Study With Pantoprazole in Obese Children and Adolescents

NCT02186652 | Completed Phase 1 Results DMC

• 1 other identifier: Pro00048765
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

Brief Summary

Multicenter, comparative single-dose pharmacokinetic (PK) study

Conditions

Gastroesophageal Reflux Disease

Keywords

obese; children; adolescents; GERD; pharmacokinetic

Outcome Measures

Primary Outcomes (9)

• Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Cmax).

  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.

  pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

• Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Tmax).

  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.

  pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

• PK Sampling

  Total number of fresh plasma samples (all participants)

  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

• Drug Concentration in Plasma Samples

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

  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

• Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).

  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.

  pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

• Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).

  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.

  pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

• Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (CL/F).

  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.

  pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

• Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).

  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.

  pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

• Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).

  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.

  pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

Secondary Outcomes (1)

• The CYP2C19 Genotype and Its Association With CYP2C19 Phenotype

  0, 1, 2, 3, 4, 6, 8, 12 hours post-dose

Study Arms (1)

Pantoprazole

OTHER

Drug: Pantoprazole

Interventions

Pantoprazole DRUG

Pantoprazole

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant is between 6 and 17 (inclusive) years of age at the time of consent
• BMI ≥95th percentile
• Diagnosis of GERD established prior to 7 days before receipt of study drug dose defined as 1 or more of the following:
• clinical symptoms consistent with GERD as determined by the investigator
• a diagnosis of erosive esophagitis by endoscopy
• esophageal biopsy with histopathology consistent with reflux esophagitis
• abnormal pH-metry consistent with reflux esophagitis
• other test result consistent with GERD
• Written informed consent from the parent or legally authorized representative/guardian and participant assent per local IRB recommendation of age-appropriate consent and assent requirements

You may not qualify if:

• Use of pantoprazole, lansoprazole, omeprazole, esomeprazole or rabeprazole within 48 hours prior to dose of study drug
• Use of fluoxetine, fluvoxamine, ketoconazole, ticlopidine, felbamate, topiramate, valproic acid, phenobarbital, carbamazepine, erythromycin, clarithromycin, grapefruit juice, verapamil, diltiazem, cimetidine, St. John's Wort, rifampin, rifapentine within seven days prior to dose of study drug
• Consumption of food after midnight on the day of the baseline visit
• Symptomatic asthma
• Type I diabetes
• History of adverse reaction to PPI
• Impaired hepatic activity as defined as any of the following: AST ≥150 IU/L, ALT ≥150 IU/L, total bilirubin ≥2.0 mg/dl, or alkaline phosphatase ≥600 IU/L
• Serum creatinine ≥2.0 mg/dL
• For females of childbearing potential, a positive pregnancy test result
• Known infection with hepatitis B, C, or HIV
• Any other condition that, in the opinion of the principal investigator, makes participation unadvised or unsafe.

Sponsors & Collaborators

• Phillip Brian Smith: lead
• The Emmes Company, LLC: collaborator

Study Sites (4)

University of Arkansas

Little Rock, Arkansas, 72202, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

• Shakhnovich V, Smith PB, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL; Best Pharmaceuticals for Children Act - Pediatric Trials Network. Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures. J Pediatr. 2018 Feb;193:102-108.e1. doi: 10.1016/j.jpeds.2017.10.011.

  PMID: 29389444 DERIVED

MeSH Terms

Conditions

Gastroesophageal Reflux; Obesity

Interventions

Pantoprazole

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chad Livingston
• Organization: Duke Clinical Research Institute

chad.livingston@duke.edu

919-668-1935

Study Officials

• Phillip B Smith, MD

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 3, 2014
• First Posted: July 10, 2014
• Study Start: June 4, 2014
• Primary Completion: September 13, 2015
• Study Completion: September 13, 2015
• Last Updated: September 17, 2019
• Results First Posted: August 5, 2019

Record last verified: 2019-09

Locations

US (4)